Antigen-Targeting Inserted Nanomicelles Guide Pre-Existing Immunity to Kill Head and Neck Cancer.

A significant challenge in cancer therapy is the identification of suitable targets that are specifically and uniformly expressed across heterogeneous tumors. The efficacy of pre-existing antiviral immunity in tumor treatment is limited by the absence of corresponding targets. This study develops a novel platform of antigen-targeted inserted nanomicelles, preS1 (an antigen of hepatitis B virus)-pHLIP nanomicelles, in which tumor-targeting nanomicelles release antigens that label tumor tissue for pre-existing immunity-mediated lysis in situ. In animal models of head and neck cancers, including head and neck squamous cell carcinoma and anaplastic thyroid cancer, preS1-pHLIP nanomicelles effectively inhibited tumor growth, recurrence, and metastasis in animals pre-immunized with preS1. This therapeutic effect is associated with an increase in the proportion of preS1-specific B cells and activated tumor-specific T cells within the tumor microenvironment. Overall, this work has engineered a nanomicelle that can disguise tumor cells as viruses and achieve tumor killing through the pre-existing antiviral immune response. This strategy presents a novel approach for treating tumors with ambiguous therapeutic target profiles.